The goal of this proposal is to test a diathesis-stress model of gene x environment (g x e) interactions in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). ADHD is one of the most common disorders of early childhood, and is characterized by a history of inattentive and hyperactive-impulsive symptoms with onset before the age of 7. The disorder often persists through adolescence and into early adulthood, disrupting many of the tasks necessary for adult development. Although a subset of children with ADHD grow out of their diagnosis, most children with ADHD symptomatology are at increased risk for later problems. The genetics of ADHD has advanced to the point of identifying candidate genes, but the identification of these genes is unlikely to answer many of the etiological questions about ADHD unless interactions with the environment are considered. As such, this proposal will test the diathesis-stress model by focusing on gene x environment interactions using molecular genetic methods and measures of psychosocial and bioenvironmental risk. Because information about pre- and peri-natal environmental risk and maternal ADHD symptomatology was obtained on a limited number of subjects at the time of testing, follow-up questionnaires targeting these data will be mailed to the families. The study utilizes both case-control and family-based association methods to test both the main effects of genotype and environment, as well as their interaction. The genotypes will include polymorphisms in the DRD2, DRD4, DRD5, DAT1, 5HTT, ADRA2C and DBH genes, with plans to add genotyping of polymorphisms in SNAP-25, HTR1B, ADRA2A, DRD1, DRD3 and COMT to ongoing data collection efforts. Measures of psychosocial and bioenvironmental risk will include parent education (a proxy for SES), family size, birth order, television exposure, maternal age at birth, season of birth, maternal smoking, drinking, or substance abuse, birth weight, and obstetric complications. This project has relevance for public health because ADHD has implications for academic and occupational success and it is associated with lower self-esteem, as well as social and emotional difficulties. Furthermore, many of the environmental risk factors explored by this study (such as maternal smoking) are preventable. Thus, better understanding of the complex genetic and environmental causes of ADHD could facilitate psychoeducation aimed at prevention, early identification, and intervention enabling better academic, psychological, and occupational outcomes. [unreadable] [unreadable] [unreadable]